Scientists prevent epilepsy-induced brain cell damage in mice

“Assuming that these structural changes are linked to cognitive impairment — and there’s a lot of data to suggest that’s true then this could provide us with a path to therapies that reduce cognitive problems in epilepsy,” says senior author Dr. Michael Wong, assistant professor of neurology, of anatomy and neurobiology, and of pediatrics.

He revealed that previous studies had suggested that seizures might damage dendrites, treelike branches that extend from a nerve cell to receive signals.

“Previous studies were helpful in suggesting that dendrite structure was being damaged, but they couldn’t prove cause-and-effect and provided only limited information on the timing and mechanisms of the processes that led to damage,” says Wong.

Led by postdoctoral fellows Dr. Ling-hui Zeng and Dr. Lin Xu, a team of researcher’s in Wong’s laboratory applied an approach known as multiphoton imaging to track brain cell changes during seizures.

The researchers used a drug to induce seizures in mice and imaged brain cells before, during and after seizures.

“Within minutes, we found changes were happening quite rapidly in the dendrites. They would become swollen and the spines would disappear. After the seizure, the swelling would go down but the spines did not return. That continued to be the case for at least 24 hours,” Wong says.

It is believed that spines may be linked to long-term potentiation, a phenomenon that makes it easier for messages to pass between nerve cells and may be essential for the encoding of memories, which means that loss of spines in seizures may impair learning.

When researchers probed the mechanisms behind the spine loss, they found seizures were causing the breakdown of actin, a molecule widely used in cell structures.

When they gave the mice a drug, FK506, prior to inducing seizures, they were able to block that breakdown.

“To follow-up, we’re going to be looking at whether we can tie these changes in dendrite structure to behavioural changes in the mice,” Woo says.

“We’re also going to be searching for drugs that can reverse this effect after a seizure happens. We would like to avoid putting epilepsy patients on a new drug all the time and hope instead to find something that can be given immediately after a seizure to prevent cognitive impairment,” he adds.